Positive feedback of the amphiregulin-EGFR-ERK pathway mediates PM2.5 from wood smoke-induced MUC5AC expression in epithelial cells

• Published in: Scientific reports Vol. 7; no. 1; pp. 11084 - 12
• Main Authors: Huang, Lingmei, Pu, Jinding, He, Fang, Liao, Baoling, Hao, Binwei, Hong, Wei, Ye, Xiuqin, Chen, Jinglong, Zhao, Jun, Liu, Sha, Xu, Juan, Li, Bing, Ran, Pixin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-09-2017; Nature Publishing Group
• Subjects: 13/1; 13/21; 13/51; 14/19; 38/1; 38/77; 631/337; 704/172/4081; 82/1; 82/51; 82/80; Amphiregulin; Chronic obstructive pulmonary disease; Epidermal growth factor receptors; Epithelial cells; Extracellular signal-regulated kinase; Feedback; Fibroblast growth factor 2; Humanities and Social Sciences; Ligands; Lung diseases; Metabolic pathways; Metaplasia; Mucin; Mucus; multidisciplinary; Obstructive lung disease; Particulate matter; Respiratory tract; Rodents; Science; Science (multidisciplinary); Secretion; Signal transduction; Smoke; Wood
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11541-1

Biomass fuel smoke is thought to contribute to chronic obstructive pulmonary disease, which is characterized by mucous cell metaplasia and enhanced mucus secretion. We investigated the effect of particulate matter (PM) with a diameter <2.5 μm (PM2.5) from wood smoke (WSPM2.5) on the expression of the most prominent secreted mucin, MUC5AC. Wood smoke was able to induce MUC5AC expression in the rat respiratory tract after 3 months of exposure. WSPM2.5 could induce MUC5AC production in both primary human airway epithelial cells and the NCI-H292 cell line. This induction process was mediated by activation of epithelial growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) signaling through an EGFR ligand-dependent mechanism. Amphiregulin (AR) was identified as the major ligand responsible for EGFR-ERK signaling activation and MUC5AC expression. In turn, EGFR-ERK pathway activation was found to contribute to the
de novo
synthesis of AR. This positive feedback loop might play an important role in a sustained mucus hypersecretion response.